This project is to study the effects of diabetes mellitus on salivary glands and their innervation. Our previous studies have shown a decrease in size of the submandibular gland of the male mouse due to diabetes. In addition, the granular tubules have less amylase granules, and less of the volume of the gland is occupied by ducts. We have observed a Schwann cell proliferation in trigeminal ganglia of the C57BL/KsJ-Db mice afflicted with diabetes mellitus. The diabetic mutants provide a useful experimental model for the evalution of these effects. The changes observed in their salivary glands and the trigeminal ganglion could be relevant to the increased caries and periodontal involvement. The secretory activity of the salivary glands, regulated by acetylcholinesterase-positive parasympathetic fibers from branches of the fifth, seventh, ninth and tenth cranial nerves, will be assessed by examining the fibers with a precise histochemical method for acetylcholinesterase. The changes in the ductal portions of the submandibular gland will be evaluated with various histocytochemical methods including immunocytochemical methods for nerve growth factor and glucagon. The extent of the peripheral neuropathy, especially as it affects the trigeminal ganglion, and trigeminal and facial nerves will be assessed with various neurohistochemical methods including those which demonstrate axonal transport and capillary permeability. The caries, plaque accumulation periodontal changes and changes observed in the tongue of the diabetic mice suggest that this mouse model may be of value in studying the oral effects of the disease.